This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Allergic asthma is a complex airway inflammatory disorder, characterized by airway hyperreactivity (AHR), eosinophil and lymphocyte infiltration into the lungs, elevated serum IgE, increased mucus hypersecretion and airway remodeling. The cellular and molecular mechanisms underlying asthma exacerbations induced by ozone are not well understood. Recent findings by several laboratories have shown that IL-17-producing T cells mediate AHR and lung inflammation following exposure of mice to ozone or other environmental pollutants. The actions of IL-17 in the lungs are multifaceted and include eliciting the recruitment of neutrophils, and inducing anti-microbial peptides by epithelial cells and polymeric immunoglobulin receptor-mediated delivery of IgA into the airways. The CD4+ [unreadable][unreadable] Th17 cells are a major source of this cytokine, but also [unreadable][unreadable] T cells have been shown to be potent source of innate IL-17. Our preliminary experiments demonstrate that allergic lung inflammation results in an increase in IL-17-producing [unreadable][unreadable] T cells residing in the lung. Such [unreadable][unreadable] T cells express the [unreadable]E[unreadable]7 integrin and are closely associated with the airway epithelium. We hypothesize that during allergic airway inflammation will result in large numbers of [unreadable]E[unreadable]7+ IL-17-producing [unreadable][unreadable] T cells in the airway epithelium that will augment airway innate immunity and result in exaggerated responses to environmental oxidant insults typified by chronic lung inflammation and increased AHR. We propose to address the following aims: (i) To characterize the response of airway-associated IL-17-producing [unreadable][unreadable] T cells during allergic airway inflammation and the role of cytokines in driving their expansion in the lung. (ii) To examine the contribution of IL-17-producing [unreadable][unreadable] T cells in ozone-induced AHR and exacerbations of allergic lung inflammation and develop novel approaches in limiting chronic lung inflammation.